Differential expression of FGFRs signaling pathway components in bladder cancer: A step toward personalized medicine

Abstract

Variations Improper activation and inappropriate expression of fibroblast growth factor receptors (FGFRs) in cancer suggests that they can act as therapeutic targets. Fibroblast growth factor receptor inhibitors are currently employed in clinical trials of different cancers. Regarding the essence and the importance of the personalized medicine, mainly mirrored by remarkable inter-individual variations in different populations, we aimed to perform a pilot study to address FGFR1 and FGFR3 expression levels and their correlation with the clinicopathological features in Iranian patients with bladder cancer (BC). Paired tumor and adjacent non tumor tissue samples along with their clinico-pathological parameters were obtained from 50 cases diagnosed with BC in different stages and grades. The mRNA expressions of FGFR1 and FGFR3 in tissue samples were determined by real-time polymerase chain reaction (real-time PCR). The expression levels of FGFR3 were significantly higher in tumor tissues when compared to adjacent normal tissues (p = 0.007), regardless of the stages and grades of the tumor. Over expression was associated with cigarette smoking (p = 0.037) and family history for cancer (p = 0.004). Decreased expression of FGFR1 was observed, remarkably evident in high-grade tumors (p = 0.047), while over expression was detected in low-grade samples. This pilot study clearly suggests that in Iranian BC patients FGFR1 and FGFR3 expression patterns are different, and also highly distinctive with regard to the tumor’s stage and grade. Such particular expression patterns may indicate their special values to be employed for interventional studies aiming targeted therapy. Further studies with a larger sample size are needed to validate our results.

Overexpression of fibroblast growth factor receptor 3 in urothelial carcinoma of urinary bladder among Iraqi patients and its correlation with different clinicopathological parameters

“…These findings underline the potential for FGFR3 as a marker for non-invasive, lower grade bladder tumors. The study also paralleled findings from other regional studies, such as Hammam et al [15] and Tavakkoly-Bazzaz J et al [16] , but unlike some studies, it found no significant correlation between FGFR3 gene amplification and tumor grade. The research, however, does affirm the significant correlation between FGFR3 expression and both tumor pathological stage and grade, suggesting a conserved pattern across different populations.…”

Role of FGFR3 in Urothelial Carcinoma

“…In an Iranian study, the authors found an increased expression of FGFR3 in most of the samples inall grades and stages (19).…”

Genetic and molecular biology of bladder cancer among Iranian patients

“…The fibroblast growth factor receptor ( FGFR ) as a tyrosine kinase receptor is one of the main regulators of cell‐cycle progression, angiogenesis, and embryonic development. It has been reported that there were FGFR1 (OMIM: 136350) and FGFR3 (OMIM: 134934) overexpressions in low‐grade and all tumors, respectively, among a subpopulation of Iranian BC subjects (Ousati Ashtiani, Tavakkoly‐Bazzaz, et al, 2017). The small G‐protein signaling modulator 3 ( SGSM3 ) (OMIM: 610440) is a GTPase involving in regulation of G‐protein and Ras signaling (Yang, Sasaki, Minoshima, & Shimizu, 2007).…”